H. pylori has been called the most common infectious disease of humans in the world today. Worldwide, between 50-100% of people are infected with H. pylori, but only a minority of those develop clinical signs of disease. Almost 2 decades of research have resulted in a general consensus that host immune response is a critical factor in determining the outcome of infection. Gastritis due to H. pylori is a T helper-1-mediated immune response associated with high levels of IFNgamma and low levels of IL-10 and other anti-inflammatory mediators. Understanding cytokine function in gastritis due to H. pylori has both diagnostic and therapeutic significance. First, identification of regulatory cytokines such as IL-10 or TGFbeta could lead to further understanding of regulatory pathways and development of therapies for those individuals with intractable infections. Second and perhaps equally important, such understanding could lead to the ability to identify individuals likely to be responders or non-responders. Individuals vary widely in their response to H. pylori, likely because of varying immunoreactivity of each individual host. Because of the strong association between IL-10 and immunoregulation of H. pylori responses, we have chosen to focus this pilot study on IL-10. Our overall goal is to test the hypothesis that recombinant murine IL-10 produced in situ by H. pylori ameliorates or prevents gastritis in mice. This goal will be accomplished in 2 specific aims: Aim 1: To engineer H. pylori to express recombinant murine IL- 10. Aim 2: To determine if in vivo expression leads to prevention or resolution of gastritis in response to recombinant bacteria or to wild-type H. pylori that co-colonize with recombinant strains. Briefly, we will construct recombinant H. pylori that expresses murine IL-10, demonstrate that the cytokine is expressed by bacteria in culture and in the mouse stomach, and determine if such expression ameliorates or prevents inflammation in a mouse model of severe gastritis. A successful outcome will not only determine the potential therapeutic role of IL-10 in gastritis due to H. pylori, but will also establish a model in which the roles of other cytokines and mediators can be determined, and host and bacterial interactions can be directly evaluated in vivo.